mixture: for 80 mg – Opadry II 85G34643 Pink (polyvinyl alcohol, talc, titanium dioxide (E 171), macrogol 3350, lecithin, red iron oxide (E 172), yellow iron oxide (E 172)).
Dosage form
Film-coated tablets.
Main physicochemical properties:
80 mg tablets: pink, round, biconvex, film-coated tablets with a breakline on both sides, a “V” logo on one side and breaklines on the sides.
Pharmacotherapeutic group
Simple angiotensin II antagonists. ATC code C09C A03.
Pharmacological properties
Pharmacodynamics
Valsartan is a potent, specific angiotensin II receptor antagonist for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the known effects of angiotensin II. Increased plasma levels of angiotensin II after blockade of AT1 receptors with valsartan may stimulate unblocked AT2 receptors, which counteract the effect of AT1 receptors. Valsartan does not exhibit any partial agonist activity at AT1 receptors, but has a much higher (approximately 20,000-fold) affinity for AT1 receptors than for AT2 receptors. There is no evidence that valsartan binds to or blocks other hormone receptors or ion channels that play an important role in cardiovascular regulation.
Valsartan does not inhibit ACE (angiotensin-converting enzyme), also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. The use of the drug in patients with arterial hypertension leads to a decrease in blood pressure without affecting the pulse rate.
The onset of the hypotensive effect is noted within 2 hours, the maximum - within 4-6 hours after oral administration; the duration of action is more than 24 hours. The maximum therapeutic effect develops 4 weeks after the start of treatment and is maintained during long-term therapy. When used with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.
Abrupt discontinuation of the drug is not accompanied by the development of withdrawal syndrome.
With long-term use of the drug in patients with arterial hypertension, it was found that the drug had no significant effect on the level of total cholesterol, uric acid, and in fasting studies - on the concentration of triglycerides and glucose in blood serum.
Heart failure
The use of the drug leads to a decrease in hospitalizations for heart failure, a slowdown in the progression of heart failure, an improvement in the functional class according to the NYHA (New York Heart Association) classification, an increase in ejection fraction, as well as a decrease in the signs and symptoms of heart failure (including dyspnea, fatigue, edema, wheezing) and an improvement in the quality of life compared to placebo.
Post-infarction state
With regard to the rate of all-cause mortality after myocardial infarction, valsartan is as effective as captopril. The rate of all-cause mortality was similar in the groups of patients receiving valsartan (19.9%), captopril (19.5%), and valsartan + captopril (19.3%). The simultaneous use of captopril and valsartan did not lead to additional beneficial effects compared with the use of captopril alone. No differences were found between valsartan and captopril in the rate of all-cause mortality, regardless of gender, age, race, treatment received at the onset of myocardial infarction, or underlying disease. Valsartan was also effective in reducing cardiovascular mortality and hospitalizations for heart failure, as well as recurrent myocardial infarction. Valsartan had a positive effect on such an indicator as the period of time after an acute myocardial infarction to the appearance of the first manifestations of cardiovascular pathology that lead to death.
Children
Hypertension: The antihypertensive effect of valsartan was evaluated in 4 randomized, double-blind clinical trials in 561 children aged 6 to 18 years and in 165 children aged 1 to 6 years. Renal and urinary disorders and obesity were the most common underlying medical conditions causing hypertension in the children included in these trials.
Clinical experience in children aged 6 years and over
In hypertensive children aged 6 to 16 years with a body weight of <35 kg, valsartan 10, 40 or 80 mg/day (low, medium and high doses) and in children with a body weight of ≥35 kg, valsartan reduced systolic and diastolic blood pressure in a dose-dependent manner at the end of 2 weeks. In total, the three valsartan dose levels (low, medium and high) significantly reduced systolic blood pressure by 8, 10, 12 mmHg from baseline, respectively.
Clinical experience in children under 6 years of age
Valsartan is not recommended for use in this age group.
Pharmacokinetics
After oral administration of valsartan tablets, peak plasma concentrations are reached in 2-4 hours, and in solution in 1-2 hours. The mean absolute bioavailability of the tablets and solution is 23% and 39%, respectively. Food reduces exposure (as determined by AUC) of valsartan by approximately 40% and the maximum plasma concentration (Cmax) by approximately 50%, although plasma concentrations of valsartan starting from approximately 8 hours after dosing are similar in the fasting and fed groups. However, the decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be taken with or without food.
Distribution
The volume of distribution of valsartan at steady state after intravenous administration is approximately 17 L, indicating that valsartan is not extensively distributed into tissues. Valsartan is extensively bound to serum proteins (94-97%), mainly to serum albumin.
Biotransformation
Valsartan is not extensively metabolized, with only approximately 20% of the dose excreted as metabolites. The hydroxymetabolite has been identified in plasma at low concentrations (less than 10% of the AUC of valsartan). This metabolite is pharmacologically inactive.
Breeding
The pharmacokinetic curve of valsartan is multiexponential (T½α <1 h and T½ß about 9 hours). Valsartan is excreted mainly via the bile with feces (approximately 83% of the dose) and by the kidneys with urine (approximately 13% of the dose), mainly in unchanged form. After intravenous administration, plasma clearance of valsartan is about 2 l/h, and renal clearance is 0.62 l/h (approximately 30% of total clearance). The half-life of valsartan is 6 hours.
In patients with heart failure (40 mg, 80 mg and 160 mg tablets)
The mean time to reach Cmax and the half-life of valsartan in patients with heart failure and in healthy volunteers are similar. The AUC and Cmax values of valsartan are almost proportional to the increase in dose above the clinical dosing range (40 to 160 mg 2 times a day). The average accumulation ratio is approximately 1.7. The estimated clearance of valsartan after oral administration is approximately 4.5 l/h. Age does not affect the estimated clearance in patients with heart failure.
Pharmacokinetics in specific patient groups
Elderly patients: In some elderly patients, the systemic exposure to valsartan was somewhat greater than in younger patients, but this has not been shown to be of any clinical significance.
Patients with renal impairment. As expected for a compound with renal clearance of only 30% of total plasma clearance, no correlation was found between renal function and systemic exposure to valsartan. Therefore, no dose adjustment is required in patients with renal impairment (creatinine clearance >10 ml/min). There are currently no safety data available in patients with creatinine clearance <10 ml/min or in patients undergoing dialysis, and valsartan should be used with caution in such patients. Valsartan is highly bound to plasma proteins and is unlikely to be removed by hemodialysis.
Patients with hepatic impairment. Approximately 70% of the absorbed dose is excreted in the bile, mainly unchanged. Valsartan is not significantly metabolized. In patients with mild to moderate hepatic impairment, valsartan exposure (AUC) was approximately doubled compared to healthy volunteers, although plasma valsartan concentrations did not correlate with the degree of hepatic impairment. There is no information available in patients with severe hepatic impairment.
Children
In a study of 26 hypertensive children (aged 1 to 16 years) receiving a single dose of valsartan suspension (mean dose 0.9-2 mg/kg, maximum dose 80 mg), the clearance (l/h/kg) of valsartan was comparable across the age range from 1 to 16 years with similar clearance in adults receiving the same drug.
Patients with renal impairment. Use in children with creatinine clearance <30 ml/min and in children undergoing dialysis has not been studied, therefore valsartan is not recommended in such patients. No dose adjustment is required in children with creatinine clearance >30 ml/min. Renal function and serum potassium should be closely monitored.
Indication
Arterial hypertension: 80 mg, 160 mg and 320 mg tablets
Treatment of arterial hypertension in adults and children aged 6 years and older.
Post-infarction condition: 40 mg, 80 mg and 160 mg tablets
Treatment of clinically stable adult patients with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction following a recent (12 hours - 10 days) myocardial infarction.
Heart failure: 40 mg, 80 mg, and 160 mg tablets
Treatment of symptomatic heart failure in adult patients when angiotensin-converting enzyme (ACE) inhibitors cannot be used, or as adjunctive therapy with ACE inhibitors when beta-blockers cannot be used.
Contraindication
Hypersensitivity to valsartan, soybean oil, peanut oil or to any of the excipients. Congenital angioedema or angioedema that developed during previous treatment with an ACE inhibitor or angiotensin II receptor antagonist. Severe hepatic insufficiency, biliary cirrhosis and cholestasis. Pregnancy or planning pregnancy (see "Use during pregnancy and lactation"). Concomitant use of angiotensin receptor antagonists, including valsartan, or ACE inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) <60 ml/min/1.73 m2). There are no data in patients with severe renal impairment (creatinine clearance less than 10 ml/min).
Interaction with other medicinal products and other types of interactions
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARA, ACE inhibitors or aliskiren
Concomitant use of ARBs, including valsartan, with other drugs that act on the RAAS is associated with an increased incidence of hypotension, syncope, hyperkalemia and changes in renal function (including acute renal failure) compared with monotherapy. Dual blockade of the RAAS through the combined use of ACE inhibitors, ARBs or aliskiren is therefore not recommended. If therapy with dual RAAS blockade is considered absolutely necessary, it should be carried out only under specialist supervision and with close monitoring of renal function, electrolytes and blood pressure.
The concomitant use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m2) (see section 4.3).
The concomitant use of ARBs, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with type 1 and type 2 diabetes.
ACE inhibitors, including valsartan, and ARBs should not be used concomitantly in patients with diabetic nephropathy.
Concomitant use is not recommended.
Lithium
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant use of ACE inhibitors. Due to the lack of experience with the concomitant use of valsartan and lithium, this combination is not recommended. If the combination is considered necessary, careful monitoring of serum lithium levels is recommended. The risk of lithium toxicity may be further increased if a diuretic is also used.
Potassium
Potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium and other medicinal products that may increase potassium levels (heparin, etc.) may lead to an increase in serum potassium levels and, in patients with heart failure, to an increase in creatinine levels. If the use of a medicinal product that affects potassium levels is considered necessary in combination with valsartan, monitoring of plasma potassium levels is recommended.
Caution is required when used concomitantly
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid >3 g/day, and nonselective NSAIDs
When angiotensin II antagonists are used concomitantly with NSAIDs, attenuation of the antihypertensive effect may occur. In addition, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function is recommended at the beginning of treatment, as well as adequate hydration of the patient.
Conveyors
In vitro studies have shown that valsartan is a substrate for the hepatic uptake transporter OATP1B1/OATP1B3 and the hepatic efflux transporter MRP2. The clinical significance of these findings is unknown. Concomitant use of inhibitors of the uptake transporter (e.g. rifampicin, cyclosporine) or efflux transporter (e.g. ritonavir) may increase systemic exposure to valsartan. Appropriate precautions should be taken when initiating or discontinuing concomitant use of these medicinal products.
Others
In drug interaction studies with valsartan, no clinically significant interactions of valsartan with the following drugs were observed: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Children
Caution is advised when valsartan is co-administered with other agents that inhibit the renin-angiotensin-aldosterone system, which may increase serum potassium levels, in children and adolescents with arterial hypertension. Renal function and serum potassium levels should be closely monitored.
Application features
Hyperkalemia
Renal impairment. There are currently no data on the safety of the drug in patients with creatinine clearance <10 ml/min and patients undergoing dialysis, therefore valsartan should be used with caution in such patients. No dose adjustment is required for adult patients with creatinine clearance >10 ml/min.
The concomitant use of angiotensin receptor antagonists, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with renal impairment (glomerular filtration rate (GFR) <60 mL/min/1.73 m2).
Hepatic impairment: Valsartan should be used with caution in patients with mild to moderate hepatic impairment without cholestasis.
Patients with sodium and/or volume depletion. In patients with severe sodium and/or volume depletion, e.g. those receiving high doses of diuretics, symptomatic hypotension may occasionally occur after initiation of valsartan therapy. Sodium and/or volume depletion should be corrected before initiating valsartan therapy, e.g. by reducing the dose of diuretic.
Renal artery stenosis. The safety of valsartan has not been established in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Short-term administration of valsartan to 12 patients with vasorenal hypertension secondary to unilateral renal artery stenosis did not cause any significant changes in renal hemodynamic parameters, serum creatinine, or blood urea nitrogen. Since other medicinal products that affect the renin-angiotensin-aldosterone system may increase blood urea and serum creatinine in patients with unilateral renal artery stenosis, monitoring of renal function is recommended as a safety precaution during treatment with valsartan.
Kidney transplantation
There are currently no data on the safety of valsartan in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism should not use Valsartan-Teva because they do not have an activated renin-angiotensin system.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, the drug should be administered with extreme caution to patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Pregnancy
Angiotensin II receptor antagonists are contraindicated during pregnancy. Unless continued therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative treatment with an approved treatment for use in pregnancy should be started.
Recent myocardial infarction
The combination of captopril and valsartan did not show any additional clinical benefit, but the risk of adverse reactions was increased compared with monotherapy with the respective drugs. Therefore, the combination of valsartan with an ACE inhibitor is not recommended.
Caution should be exercised in patients after myocardial infarction. Evaluation of patients after myocardial infarction should always include assessment of renal function.
The use of valsartan in patients after myocardial infarction often results in some reduction in blood pressure, usually leading to the need to discontinue therapy due to ongoing symptomatic hypotension, provided that the dosage instructions are followed.
Heart failure
The risk of adverse reactions, especially hypotension, hyperkalemia and decreased renal function (including acute renal failure), may be increased when valsartan is used in combination with an ACE inhibitor. In patients with heart failure, the triple combination of an ACE inhibitor, a beta-blocker and valsartan has not shown any clinical benefit. This combination is likely to increase the risk of adverse effects and is therefore not recommended. The triple combination of an ACE inhibitor, a mineralocorticoid receptor antagonist and valsartan is also not recommended.
Such combinations should only be used under specialist supervision and with careful monitoring of kidney function, electrolyte levels, and blood pressure.
Studies on the safety and efficacy of Valsartan-Teva in children have not been conducted.
History of angioedema
Angioedema, including laryngeal and glottis edema resulting in airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue, has been reported in patients treated with valsartan; some of these patients had previously experienced angioedema while taking other drugs, including ACE inhibitors. The development of angioedema requires immediate discontinuation of valsartan, and the drug should not be re-administered.
In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and in isolated cases with acute renal failure and/or fatal outcome. Since valsartan is an angiotensin II antagonist, it cannot be excluded that the use of Valsartan Teva may be associated with impaired renal function.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Concomitant use of ARA drugs, including valsartan, with other drugs that affect the RAAS is associated with an increased incidence of hypotension, hyperkalemia, and changes in renal function compared with monotherapy. Monitoring of blood pressure, renal function, and electrolytes is recommended in patients receiving valsartan and other drugs that affect the RAAS.
Children
Renal impairment. Use in children with creatinine clearance <30 ml/min and in children undergoing dialysis has not been studied, therefore valsartan is not recommended for use in such patients. No dose adjustment is required for children with creatinine clearance >30 ml/min. Renal function and serum potassium should be closely monitored during treatment with valsartan. This applies in particular to cases where valsartan is used in the presence of other conditions (high fever, dehydration) that are likely to impair renal function. The concomitant use of angiotensin receptor antagonists, including Valsartan, or ACE inhibitors with aliskiren in patients with renal impairment (glomerular filtration rate (GFR) <60 ml/min/1.73 m2) is contraindicated.
Hepatic impairment. As in adults, Valsartan is contraindicated in children with severe hepatic impairment, biliary cirrhosis and patients with cholestasis. There is limited clinical experience with valsartan in children with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in such patients.
Galactose intolerance, lactase deficiency or glucose-galactose malabsorption
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Lecithin
This medicine should not be used in patients with hypersensitivity to peanut or soya.
Sunset yellow FCF (E110) dye
Valsartan-Teva tablets, 320 mg, contain the dye Sunset yellow FCF (E110), which may cause allergic reactions.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects on the ability to drive and use machines have been conducted. It should be taken into account that dizziness or weakness may occur when driving or using other machines.
Use during pregnancy or breastfeeding
Pregnancy
The use of angiotensin II receptor antagonists (AIIRAs) is contraindicated during the entire period of pregnancy, as well as in women planning a pregnancy.
Epidemiological data on the risk of teratogenic effects following exposure to ACE inhibitors during the first trimester of pregnancy are inconclusive, but a small increase in risk cannot be excluded. Since there are no controlled epidemiological data on the risk with angiotensin II receptor antagonists, a risk of teratogenic effects may also exist for this class of drugs. Unless continued therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative treatment which is approved for use in pregnancy should be started.
It is known that the use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy induces human fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
If AIIRAs have been used from the second trimester of pregnancy, ultrasound examination is recommended to check kidney function and the condition of the skull bones.
Newborns whose mothers have taken AIIRAs should be closely monitored for the development of hypotension.
Breastfeeding period
Because no information is available regarding the use of valsartan during breastfeeding, Valsartan Teva is not recommended for use in breast-feeding women. Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Fertility
Valsartan did not cause adverse reproductive effects in rats at doses up to 200 mg/kg/day, which is 6 times the maximum recommended human dose on a mg/m2 basis (calculated for an oral dose of 320 mg/day in a 60 kg patient).
Method of administration and doses
Method of application
Valsartan-Teva can be taken regardless of meals; the tablets should be swallowed with water.
Dosage
Arterial hypertension
The recommended starting dose of valsartan is 80 mg once daily. The antihypertensive effect is achieved within 2 weeks and the maximum effect is achieved within 4 weeks. In some patients with inadequately controlled blood pressure, the dose may be increased to 160 mg and to a maximum of 320 mg.
Valsartan Teva can also be used with other antihypertensive agents. Concomitant use of diuretics such as hydrochlorothiazide will further reduce blood pressure in such patients.
Recent myocardial infarction
Treatment can be started as early as 12 hours after myocardial infarction in clinically stable patients. After an initial dose of 20 mg valsartan twice daily, the dose should be increased to 40 mg, 80 mg and 160 mg twice daily over the next few weeks. The initial dose should be administered as a 40 mg tablet, which can be divided into equal doses. The target maximum dose is 160 mg twice daily. In general, it is recommended that the dosage level of 80 mg twice daily be reached 2 weeks after the start of treatment and the maximum dose of 160 mg twice daily be reached after 3 months, depending on the patient's tolerability of the treatment. If symptomatic arterial hypotension or renal dysfunction occurs, a dose reduction should be considered.
Valsartan can be used in patients who have been treated with other drugs after myocardial infarction, such as thrombolytics, acetylsalicylic acid, beta-blockers, statins and diuretics. Combination with ACE inhibitors is not recommended.
Patients after myocardial infarction always need to have their kidney function monitored.
Heart failure
The recommended starting dose of valsartan is 40 mg twice daily. Dose increases to 80 mg and 160 mg twice daily should be made at intervals of not less than 2 weeks to the highest dose, depending on the patient's tolerance. A reduction in the dose of concomitant diuretics should be considered. The maximum daily dose used in clinical trials was 320 mg, divided into several doses.
Valsartan can be used in combination with other drugs for the treatment of heart failure. However, the triple combination of an ACE inhibitor, valsartan and a beta-blocker or a potassium-sparing diuretic is not recommended. Monitoring of renal function is necessary in patients with heart failure.
Application to specific patient groups
Elderly patients
Elderly patients do not require dose adjustment.
Kidney failure
No dose adjustment is required in adult patients with creatinine clearance >10 ml/min. Concomitant use of valsartan with aliskiren is contraindicated in patients with renal impairment (GFR <60 ml/min/1.73 m2).
Diabetes mellitus
Concomitant use of valsartan with aliskiren is contraindicated in patients with diabetes mellitus.
Liver failure
Valsartan-Teva is contraindicated in patients with severe hepatic impairment, biliary cirrhosis and patients with cholestasis. For patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg.
Arterial hypertension in children
Children and adolescents aged 6 to 18 years
The initial dose is 40 mg once daily for children weighing less than 35 kg and 80 mg once daily for children weighing 35 kg or more. The dose should be adjusted based on blood pressure response. The maximum doses studied in clinical trials are shown in Table 1.
Doses above these have not been studied and are therefore not recommended.
Table 1
Body weight
Maximum dose of valsartan
From ≥18 kg to <35 kg
80 mg
From ≥35 kg to <80 kg
160 mg
From ≥80 kg to ≤160 kg
320 mg
Children under 6 years old
The safety and effectiveness of valsartan in children aged 1 to 6 years have not been established.
Use in children aged 6 to 18 years with renal insufficiency
Use in children with creatinine clearance <30 ml/min and in children undergoing dialysis has not been studied, therefore valsartan is not recommended for use in such patients. No dose adjustment is required for children with creatinine clearance >30 ml/min. Renal function and serum potassium levels should be closely monitored.
Use in children aged 6 to 18 years with hepatic impairment
As in adults, Valsartan is contraindicated in children with severe hepatic impairment, biliary cirrhosis and patients with cholestasis. Clinical experience with valsartan in children with mild to moderate hepatic impairment is limited. The dose of valsartan should not exceed 80 mg in such patients.
Heart failure and recent myocardial infarction in children
Valsartan is not recommended for the treatment of heart failure or recent myocardial infarction in children due to a lack of data on safety and efficacy.
Valsartan-Teva can be used to treat hypertension in children aged 6 years and older. The safety and efficacy of valsartan in children aged 1 to 6 years have not been established. The drug is not recommended for the treatment of heart failure or post-infarction conditions in children due to a lack of data on safety and efficacy.
Overdose
Symptoms: Overdose with valsartan may result in severe hypotension, which may lead to depression of consciousness, vascular collapse and/or shock.
Treatment. Therapeutic measures depend on the time of administration and the type and severity of symptoms; stabilization of the circulatory system is of paramount importance. If hypotension occurs, the patient should be placed in the supine position and volume should be corrected. Valsartan is unlikely to be removed by hemodialysis.
In controlled clinical trials in adult patients with hypertension, the incidence of adverse reactions with placebo was similar to that with valsartan. The incidence of adverse reactions was not related to dose or duration of treatment, and there was no association with gender, age, or race.
Adverse reactions reported during clinical, post-marketing and laboratory studies are listed below by system organ class.
A cumulative search of the safety data system was performed for adverse reactions in the categories “very rare”, “rare” and “uncommon” that were not detectable in clinical trials.
The frequency of adverse reactions is estimated as follows: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/100000), including isolated reports. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions reported during post-marketing and laboratory studies for which it is not possible to determine the frequency of adverse reactions are listed with a frequency of "not known".
